Significance Chronic social and psychological stressors, prevalent in modern society, are important determinants of health and welfare. This research investigates, in highly social primates the consequences of social and environmental perturbations that challenge restoration of homeostasis and lead to lengthy periods of altered pituitary-adrenal regulation. Objectives This is a new program of research that is designed to evaluate the cognitive, immunological, and neurobiological consequences of stressors that produce chronic elevations and chronic reductions in pituitary-adrenal activity in New World monkeys. Results Much of the immunological and neurobiological research in chronic stress has relied on pharmacological manipulation of glucorticoid levels. The assumption of this research, that it is stress-induced elevations in glucocorticoids that account for health risks associated with stress, has rarely been tested directly. Our research will capitalize on a broad-based understanding of the social interactions of New World monkeys and the evidence that alterations in the social situations of these monkeys provides naturalistic models of chronic stress. We have identified two simple social manipulations that result in long-term disruption of pituitary-adrenal regulation. Mate separation in titi monkeys produces long-term elevations in cortisol; group formation in squirrel monkeys produces long-term reductions in cortisol. Comparison of the two species affords a unique opportunity to ask whether chronic stress subsumes multiple distinct syndromes, each associated with its own symptoms and risks. Future Directions We will begin detailed comparison of cognitive performance (using computer-assisted behavioral testing) and immunological competence in animals with chronically elevated or reduced glucocorticoids.. Plans also include comparison of hippocampal structure and function in animals that have been subjected to chronic stress.